High-grade glioma is a devastating disease that leaves the majority of its victims dead within 2 years. To meaningfully increase survival, a trimodality approach of surgery, radiation, and chemotherapy is needed. Carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea) is a nitrosourea alkylating agent that exerts its antitumor effect by akylating DNA and RNA. Systemic administration of nitrosoureas as a single agent or as part of procarbazine/3-cyclohexyl-1-nitroso-urea/vincristine has demonstrated little efficacy in the treatment of high-grade glioma. The development of carmustine wafers (Gliadel((R)) Wafer) as a method for controlled released delivery of carmustine from biodegradable polymer wafers enhances the therapeutic ratio by fully containing the drug within the confines of the brain tumor environment while minimizing systemic toxicities. Preclinical and clinical studies have proven the safety and efficacy of Gliadel in the management of glioblastoma. From these results, Gliadel is currently approved for use in patients with recurrent glioblastoma as an adjunct to surgery and in newly diagnosed patients with high-grade glioma as an adjunct to surgery and radiation. Other promising advances in the use of locally delivered chemotherapy for CNS malignancies, including Gliadel for brain metastases and combination therapies with systemic or biologic agents, are discussed.